2 I. Syngenta Comments on Preliminary Work Plan

(1) Syngenta comments in response to EPA statements: Guideline Number 835.4100,
Aerobic soil metabolism ; Page 4, Table 1.

Enclosed with this submission is data that has not been previously submitted to EPA to address this anticipated data need.

EPA Response:

EFED received the referenced study/overview under MRID numbers 49139001 and 49139002 and the study is under review. Until the review is complete and the study is classified as acceptable, the anticipated data requirement for OSCPP Guideline 835.4100 remai ns.

A quick examination of the submitted study shows that the level of un

- extracted/un

- identified
residues increases to a range of 28

- 48%. Furthermore, it appears that not all of E F E D ’s concerns
about the un

- extracted residues were addressed in the refere nced submittals. Please refer to Un

extractable Residues section on pages 19 to 22 of the Registration Review Preliminary Problem
Formulation document and EFED conclusion: “In the absence of data on identity/toxicity of un

extracted residues, these residu es will be included as part of the stressor

. ”

(2) Syngenta comments in response to EPA statements: Guideline Number 835.4400, Anaerobic aquatic metabolism ; Page 4, Table 1.

This anticipated data need is being addressed within the enclosed data submitted here in.

EPA Response:

A s s t a t e d p r e v i o u s l y , EFED has received an overview document of an anaerobic and aerobic soil metabolism study (MRID 4913900 )

. [ EFED concurs with Syngenta ’s statements on page 4 of the
referenced overview document concerning the anticipated data requirements for an anaerobic aquatic study

. On page 4 of this is overview d o c u m e n t

, Syngenta stated : “ Regarding the proposed data gap for the anaerobic aquatic sediment metabolism (EPA Guideline835.4400), Syngenta concurs with the EPA that degradation of prometryn under these conditions is very likely to be long (essentially stable) as found under anaerobic soil me tabolism conditions (included within the new aerobic soil metabolism study being submitted). Thus, Syngenta accepts the EPA's proposal to deem prometryn stable under anaerobic aquatic sediment conditions rather than conduct a new study

. ]3 Based on t he information provided by Syngenta, E F E D will assume that prometryn is stable under anaerobic aquatic sediment conditions . Therefore, the anticipated data requirement for an anaerobic aquatic study is no longer needed for the prometryn registration review

.

II. Syngenta Comments on Registration Review Problem Formulation for Prometryn

(1) Syngenta Comment in response to EPA statement, “ Furthermore, there are fifteen 24C Special local need (SLN) labels; ” Page 6, Section 2, 2nd paragraph.

There is a Caparol 4 L 24C label in OR for control of weeds on the following crops grown for seed: carrots, parsley, and coriander (EPA SLN No. OR

- 040002) that is not included in the list provided.

EPA Response:

EPA will update the list of SLN registration s when the PRA is initiated.

(2) Syngenta Comment in Response to EPA Statement, “Pre

- plant 4 inches incorporated , Notes & Restrictions.” Celery/Direct seeded crop; Product(s), Notes & Restrictions: Caparol 4L, Prometryn 4L, Cotton

- Pro, and Prometryne 4L (Agri

- solutions/ Loveland); CA only

The Caparol 4L label specifies that this use pattern may be used in AZ, CA, and NM on ly. We
believe tha t this should be reflected in the Notes & Restrictions Column.

EPA Response:

The Agency has verified that the current Syngenta Caparol 4 L label (9/27/2001) specifies that preplant incorporation is limited to AZ, CA, and NM. E F E D wi ll use the most current label information for development of the PRA. The Agency will also work with Syngenta (and other registrants) to achieve label clarity prior to initiation of the PRA.

(3) Syngenta Comment in Response to EPA Statement: “Pre

- or post

- emergence Winter application for bedded land to be planted cotton; MSR MYR 1.6”

The Caparol 4L label allows a maximum single application rate of 2.4 lb AI/A on medium or fine soil. We believe that the MSR (maximum single rate) and MYR (maximum yearly rate should be listed as 2.4 instead of 1.6.

EPA Response:4 The Syngenta Caparol 4L label appears to allow a rate of 2.4 lb ai/A for pre

- emergence application to certain soils (p. 15). The labe l also states, “Do not apply a second postemergence application of Caparol 4L or injury may occur.” E F E D will use the most current label information for development of the PRA. The Agency will also work with Syngenta (and other registrants) to achieve lab el clarity prior to initiation of the PRA.

(4) Syngenta Comment in Response to EPA Statement, “ Post

- emergence directed” and
“Chemical hoe (emerged weeds only) ” (Table 1 , rows G & H on pages 7 & 8 of the problem formulation)

On the Caparol 4L label

, “chemical hoe” and “lay

- by” are meant to be two sub

- categories of “postemergence

- directed.” Specific use rates are not provided under the main head in g but
rather under the sub

- headers for “chemical hoe” and “lay

- by

. ” The use patterns in Table, row (G) Post Emergence directed are actually for chemical hoe.

Because of this, we believe that the title for row (G) should be changes from “Postemergence directed” to “Chemical hoe (emerged weeds only ), ” and that row (H) should be removed. However, the maximum n umber of applications for chemical hoe should be changed to 3 and the maximum yearly rate should be changed to 1.5 and 2.1.

EPA Response: The Agency appreciates Syngenta ’s clarification of the Caparol 4L label , the directions for use

, post

- emergence directed application

, in the comments to the public docket. The problem
formulation

, Table 1 , rows ( G ) & ( H ) on pages 7 & 8 , should read as follows:

The Agency will work with Syngenta (and other registrants) to achieve label clarity prior to
initiation of the PRA

. ( G) Post

- e mergence directed: * In cotton 3

- 6 inches tall, be extremely careful to avoid spray contact with cotton leaves by applying Caparol 4L with a precision applica tor equipped with fenders or shields ; * In cotton <10” tall, apply only if cotton is bedded or flat

- planted.

(a) Chemical Hoe (emerged weeds only): * Minimum cotton plant Height = 3

- 6” and maximum weed Height= <1”;

OR 0.5 3 1.5 NS Use only in AR, LA, MO, MS, TN and TX

* Minimum cotton plant Height = >6” and maximum weed Height= <2” 0.7 3 2.1 NS Use in all other cotton regions (b ) Lay

- By (emerged and germinating weeds) * Minimum cotton plant Height = > 12 ” and maximum and weed Height= <2” 1.6 1 1.6 N/A No use or lower use rates depend on location, soil texture, and/or weed size5 (5) Syngenta Comment in Response to EPA Statement, “Lay

- By, MSR 1.6; MNA 1; MYR 3.2” (Table 1 on page 8 of the problem formulation, row I)

In the lay

- by section, the Caparol 4L label specifies that this application be made once per season. We believe that the MNA (maximum number of applications) should be listed as 1 instead of 2, and the MYR should be listed as 1.6 inst ead of 3.2.

EPA Response:

E F E D concurs with Syngenta’s comment . The rate should be as shown in the Table above (refer to item 4, above).

(6) Syngenta Comment in Response to EPA Statement, “Celery/Seedbeds; Product(s), Notes & Restrictions: Caparol 4L, Prometryn 4L, Cotton

- Pro, and Prometryne 4L (Agri

- solutions/Loveland); FL only” (Table 4 on page 9 of the PF)

The Caparol 4L label includes this use pattern under the section “Celery, Chinese celery

, Florence fennel; Seedbeds;” however, it does not contain a regional restriction that allows this application to be made in FL only. We believe that this should be clarified in EFED’s Table 4 so that this regional restriction is not listed for Caparol 4L.

EPA Response:

Althoug h the Syngenta Caparol 4L labels states no regional restrictions , labels for products registered to other companies ( E P A R e g

. N u m b e r s 3 4 7 0 4

- 6 9 2 a n d 9 7 7 9

- 2 9 7 ) bear the regional restriction, FL only. The Agency will work with Syngenta (and other registrants) to achieve label clarity prior to initiation of the PRA.

(7) Syngenta Commen t in Response to EPA Statement, “ Celery/Direct seeded crop; Product(s), Notes & Restrictions: Caparol 4L, Prometryn 4L, Cotton

- Pro, and Prometryne 4L (Agri

- solutions/Loveland); CA only” (Table 4 on p.9 of the PF)

The Caparol 4L label includes this use pat tern under the section “Celery, Chinese celery

, Florence fennel; Direct Seeded Crop;” however, it does not contain a regional restriction...for CA only. We believe that this should be clarified in EFED’s Table 4 so that the regional restriction is not liste d for Caparol 4L.

EPA Response:

Although the Syngenta Caparol 4L labels states no regional restrictions, labels for products registered to other companies ( E P A R e g

. N u m b e r s 3 4 7 0 4

- 6 9 2 a n d 9 7 7 9

- 2 9 7 ) bear the regional6 restriction, CA only. The Agency will work with Syngenta (and other registrants) to achieve label clarity prior to initiation of the PRA.

(8) Syngenta Comment in Response to EPA Statement, “ Celery/Transplanted crop; Product(s), Notes & Re strictions: Maximum rate is for HI; lower use rates depend on location (Lower rates for CA, TX, FL, MI, OH and WI) and soil texture (Lower rates for coarse textured/low OM soils) ” (Table 4, page 10 of the PF)

The “Product(s), Notes & Restrictions” column does not specify which product labels contain the use pattern, but the application rates listed are inconsistent with those found on the Caparol 4L label. We believe that the “Products, Notes & Restrictions” column should be revised to list which products contain this use pattern and Caparol 4L should not be listed.

EPA Response:

Please note that what was listed in Table 4 of the PF covers the maximums for all labels including labels for products registered to other companies (higher rates and different restrictions) . However , for Caparol 4L and as per page 24 of the label, the following applies:

(9) Syngenta Comment in Response to EPA Statement, “ Celery Group/Chinese celery and Florence fennel: Pre crop emergence/at or shortly after planting OR Post crop emergence @ 2

- 5 true leaves crop stage and weeds <2” tall; Product(s), Notes & Restrictions: Caparol 4L and Prometryn 4L; CA only” (Table 4, p 10 of PF)

The Caparol 4L label inc ludes this use pattern; however , it does not contain a regional
restriction. We believe that this should be clarified in EFED’s Table 4 so that this regional restriction is not listed for Caparol 4l.

EPA Response:

Please note that what was listed in Table 4 of the PF covers all labels including labels for products registered to other companies

. However, for Caparol 4L and as per page 24 of the label, the following applies: Celery/Transplanted crop: Post

- transplant during the 2

- 6 week period after transplanting and weeds <2” tall 2.0 1 2.0 NA For Caparo l: Maximum rate is for AZ, CA, TX, MI, OH and WI; lower use rates depend on location and soil texture (lower rates for FL and coarse textured soils and soils with low OM

Celery, Chinese celery, Florence fennel: Pre crop emergence/ at or shortly after planting O R Post crop emergence @ 2

- 5 true leaves crop stage and weeds<2” tall 1.6

O R 1.0 1

1 1.6

1.0 N/A

N/A No regional restrictions for Caparol 4L but it is not to be used on sand or loamy sand soils7 E F E D appreciates Syngenta’s comments on the PF and these comments will be taken in consideration along with existing label language in determining application parameters for future
risk assessments. In the PF document, E F E D requested additional information concerning the use pattern for Caparol 4 L (please refer to page 11 of the EFED Registration Review Preliminary

Problem Formulation ) , including the following:

(1) The maximum yearly rate for each application type, i.e., the nine application types stated in the 1 st column of Table 1 , above, use site such as “TX” and/or soil (e.g., sandy loam soil)/cotton plant height (e.g., cotton 3

- 6”) /weed size (e.g., Weeds <2”) ;

(2) Which types of applications may be combined within the year; and

(3) Missing information (marked by NS or ?) which are necessary for exposure modeling and for inclusion in future labels.

For Suprend TM Herbicide, the label states “ Do not exceed a total of 2.7 lbs./A of Suprend per

season from all applications” (that is 2.14 lbs a.i “prometryn”/A) and continue s to state “Do not exceed 5.15 lbs. active ingredient of prometryn per acre per season resulting from all applications of Suprend TM or Caparol 4L, or other prometryn containing product s”. The registrant is requested to modify the statements above to clarify if the seasonal rate or the yearly rate is 2.14 lbs a.i of prometryn/A/season “assume: year” or 5.15 lbs a.i of prometryn/A/season “assume: year”.” For modeling purposes, E F E D assumes the maximum possible number of applications/year and the minimum application intervals, if this information is missing. Therefore, the information on which applications may be combined is important and a maximum rate per year for each crop should be included in the label.

(10) Syngenta comments in response to EPA statements: Aqueous photolysis half

- life (25°C): Stable; Page 16, Table 6.

Prometryn is photodegraded more rapidly in natural waters with half

- lives ranging from 16 to 109 days, whic h provides a more realistic input for exposure modeling. Wallace, et al. (2010)1.

EPA Response :

Photolysis in natural waters will be included in characterization; however, as per modeling parameters guidance, the aqueous photolysis half

- life at 25 o C will be used in modeling. Please refer to: http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm for more information on this guidance.

(11) Syngenta comment s in response to EPA statements: half

- lives for Aerobic Aquatic Metabolism (total system) in River and Pond Systems; Page 17, Table 7

There is a third half

- life value available, 38 days (EU

- FOOTPRINT Pesticide Properties Database (Functional TOOls for Pesticide Risk assessment and management) that should be considered. EU

FOOTPRINT is a research project funded by the European Commission as part of its 6th Framework Programme for Research and Technological Development (FP6). http//www.eu

- footprint.org/pp db.html.8 Specific data cited here is also found in: Tomlin, C.D.S. 1997. The Pesticide Manual: A World Compendium, 11 th ed. Publisher: British Crop Protection Council. ISBN 978

- 1

- 901396

- 18

- 8. 1457 p.)

EPA Response:

The referenced values may be included i n characterization; however, only results from acceptable studies are used for modeling.

(12) Syngenta comments in response to EPA statements: Soil

- Water Partition Coefficients (K FOC ) L/Kg; Page 17, Table 7 and Statements on mobility of the chemical on Page 18, Paragraph 4 (two Comments)

.

First Comment: There are additional Koc values available for prometryn from a column leaching study and in the open literature:

• EPA guideline Koc values from the batch equilibrium study (MRID 41875901): 246, 169, 117, 448 mL/g

• EPA guideline Koc value from the column leaching study (MRID 41875904): 1228 mL/g

• Koc values reported by Rao and Davidson (1982) 2 : 56.9, 100.0, 194.1, 200.0, 202.9, 207.9, 239.1, 264.7, 272.3, 292.4, 299.4, 320.5, 323.9, 327.3, 348.6, 355.4, 380.4, 386.7, 415.3, 444.4, 471.2, 503.0, 504.4, 507.9, 508.3, 528.9, 606.5, 607.8, 610.0, 637.5, 826.9, 865.4, 918.6, 1067.6, 1362.2, 1775.0, 2388.4, 3013.9 mL/g

• Koc value reported by Seol, et al. (2000) 3 : 400 mL/g

• Koc values reported by Baskaran and Kennedy (1999) 4 : 483, 254, 432 mL/g

Koc values reported by Turin and Bowman (1997) 5 fall in the overall range of soil adsorption characteristics, but were not included in the calculation of Koc model input because the individual Koc values were not reported in the publication, only the range (190

- 617 mL/g).

Second Comment: The discrepancies can be explained by correlating organic carbon content for soil used in the column leaching study with available Kd values, as the study by Rao and Davidson (1982) 2 indicated that soil adsorption (Kd) correlated linerally with percent organic carbon (%OC). Using the
linear correlation relationsh ip derived from Rao and Davidson (1982) 2 for the California sandy loam (0.407% OC) used in the column leaching study, a Koc value of ~1307 mL/g may be calculated. Based on batch equilibrium soil adsorption, column leaching and open literature data, prometr yn soil adsorption ranges between 57 mL/g and 3014 mL/g. Using the mobility classification presented by FAO (2000) 6 , prometryn would range from ‘slightly mobile’ to ‘mobile’. The mean Koc value (577 mL/g) from laboratory, batch equilibrium, soil column lea ching and open literature data falls in the ‘moderate mobility’ class (FAO, 2000) 6 and therefore, less likely to be transported into surface and ground waters.

EPA Response:
EFED will consider the additional Koc Values referenced in Syngenta’s comments when determining the appropriate adsorption/desorption values for characterization and modeling (K oc Vs K d ). In this respect, it is noted that only values from acceptable adsorption/desorption studies are used for modeling ; as per the per modeling paramet ers guidance

.9 (13) Syngenta comment in reference to EPA Statement , “Freshwater fish Acute: Rainbow Trout (Oncorhynchus mykiss), 96

- hr LC 50 = 2.91 mg/L” p. 24, Table 9 :

MRID 0070686 was completed in 1965, prior to the development of standardized test guidelines, and hence the methods used for the test were not consistent with current guideline specifications. In particular, the prometryn exposure concentrations were not measured, dissolved oxygen and pH were not reported, water temperature reached 17. 2° C (OPPTS 850.1075 recommends 12 ± 2 ° C for rainbow trout), and temperature deviated by a ran ge of
4.4° C in some treatments (OPPTS 850.1075 recommends ± 1 ° C). Syngenta believes that data from the more recent rainbow trout acute study (Hamaker 1985a, MRID 49076601) are more reliable and accurate and therefore should be used in the assessment. The endpoint for the Hamaker 1985a study is 5.46 mg/L.

EPA Response:

MRID 49076601 is currently undergoing Agency review. During the development of the preliminary risk assessment ( PRA ) , the Agency will determine which rainbow trout stud y is appropriate for use.

(14) Syngenta comment in reference to EPA Statement, “Freshwater invertebrate Acute: Water flea (Dapnia magna), 48

- he EC 50 = 9.70 mg/L” p. 24, Table 9:

Syngenta believes that due to data quality concerns associated with Marchini et al. (1988) (e.g., no raw data, no control data, actual exposure treatments not described (neither number of treatments nor concentration), test concentration were not analytically confirmed (stocks measured but no data provided or discussed and cannot be verified because raw data was not provided) that the freshwater invertebrate acute endpoint should be based on data from the D. magna GLP study (Hamaker 1985b, to be submitted following these comments).

EPA Response:

The Hamaker 1985b, to be submitted by Syngenta following these comments, will be reviewed during the development of the PRA. At that time, t he Agency will decide which studies are appropriate for use in the assessment.10 (15) Syngenta comment in reference to EPA Statement , “Green Algae: Selanastrum capricornutum 7

- d IC 50 = 11.6 μg/L” p.25

- 26, Table 10:

Syngenta believes that the value should be 23 μg/L as indicated in the study report.

EPA Response:

The study report indicates the 4

- d is IC 50 = 11.6 μg/L and the 7

- d is IC 50 = 23 μg/L. A 4

- day algal toxicity study is the standard test length used by the Agency and thus the 4

- d IC 50 w ill be
used in the assessment.

(16) Syngenta comment in reference to EPA Statement, “Terrestrial plants Seedling Emergence and Vegetative Vigor: Monocots + Dicots EC 25 values” p. 28, Table 11:

There appear to be inconsistencies between the endpoint values in the study reports (MRID 41035903, 410359 04) and those provided in the preliminary problem formulation 9

- 10. Syngenta lists the endpoints in a pending report “Review and Assessment of the Potential Impact of Prometryn on Federally Threatened California Red

- legge d Frog (Rana aurora draytonii) . T he following briefly describes how endpoints were reanalyzed. An attempt was made to fit three non

- linear models (logistic, extreme value and Gumbel) to dry weight data from each trial from both the vegetative vigor and seedling emergence studies (see Equa tions 1, 2 and 3 below). In some cases, rate

- response was not evident, and the sigmoidal (s

- shaped) models could not converge with the data. Model fitting was conducted with SAS software® (SAS Version 9.1), using the PROC NLIN procedure, a non

linear reg ression approach, which minimizes the sum of squared error terms. Rate (lb a.i./A) data were log transformed (base 10) based on visual inspection. The measure of effect (dry weight) was converted to an estimated response, calculated as the proportion redu ction in dry weight of each replicate relative to the mean of control replicates for the trial.11 Of the models providing the lowest error (lowest sum of squared error terms (SSE)), the most sensitive EC25 metric was selected for each species in each study unless the estimated response for the trial was greater than 50% at the first treatment level. If this was the case, the trial was not considered for EC25 estimation (this only occurred for the 2nd cucumber trial from the vegetative vigor study). A regr ession approach was taken to fitting parametric species sensitivity distributions (SSDs). Median plotting positions were used to assign observed proportion of species to the ordered EC25s with Filiben’s approximation to the median for inner values (Aldenb erg et al., 2002)12. Log logistic, extreme value and gumbel models (see Equations 1, 2 and 3) were fit to these observed proportion of species affected (EC25s exceeded) versus the rate of deposition (lb a.i./A) using PROC NLIN nonlinear procedure in SAS S oftware (SAS Version 9.1).

Summary of terrestrial plant EC25 estimates for dry weight with various crop species Study Species Trial EC25 Estimate (lbs
SE Cabbage 2 0.0155
SE Lettuce 2 0.0578
SE Cucumber 1 0.0768
SE Onion 1 0.110
SE Oat 1 0.115
SE Ryegrass 1 0.179
SE Tomato 1 0.195
SE Soybean 1 0.299
SE Corn 1 0.427
SE Carrot 1 1.99

VV Cucumber 1 0.004

VV Lettuce 2 0.008

VV Cabbage 1 0.085

VV Tomato 1 0.130

VV Onion 1 0.164

VV Soybean 1 0.184

VV Corn 1 0.754

VV Oat 1 1.34

VV Carrot 1 >1.6

VV Ryegrass 1 >1.6 SE = Tier II Seedling Emergence, VV = Tier II Vegetative Vigor

EPA Response:

The Agency appreciates Syngenta’s analysis of endpoints regarding MRID 41035903 and 41035904. During the development of the PRA

, E F E D will rerun the statistics using CETIS, updated software, to ensure the derivation of endpoints is consistent across studies. CETIS

,12 Comprehensiv e Environmental Toxicity Information System, is a commercial software program designed to statistically compare responses at each tested chemical concentration to the responses of the controls in order to determine the NOAEC (No Observed Adverse Effects
Co ncentrat ion) and LOAEC (Lowest Observed Adverse Effects Concentration), as well as to estimate LC (Lethal Concentration), EC (Effect Concentration), and IC (Inhibition Concentration) values at the 5%, 10%, 25%, and 50% levels. CETIS has been specifically customized to store and analyze (EFED) study data according to current standard procedures. CETIS has replaced all EFED statistical programs used to conduct data evaluation reviews on
standar d laboratory toxicity st udy data

.